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匹配条件: “ Dirk H. Busch” ,找到相关结果约152380条。
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Presentation of an Immunodominant Immediate-Early CD8+ T Cell Epitope Resists Human Cytomegalovirus Immunoevasion
Stefanie Ameres,Josef Mautner,Fabian Schlott,Michael Neuenhahn,Dirk H. Busch,Bodo Plachter,Andreas Moosmann
PLOS Pathogens , 2013, DOI: 10.1371/journal.ppat.1003383
Abstract: Control of human cytomegalovirus (HCMV) depends on CD8+ T cell responses that are shaped by an individual's repertoire of MHC molecules. MHC class I presentation is modulated by a set of HCMV-encoded proteins. Here we show that HCMV immunoevasins differentially impair T cell recognition of epitopes from the same viral antigen, immediate-early 1 (IE-1), that are presented by different MHC class I allotypes. In the presence of immunoevasins, HLA-A- and HLA-B-restricted T cell clones were ineffective, but HLA-C*0702-restricted T cell clones recognized and killed infected cells. Resistance of HLA-C*0702 to viral immunoevasins US2 and US11 was mediated by the alpha3 domain and C-terminal region of the HLA heavy chain. In healthy donors, HLA-C*0702-restricted T cells dominated the T cell response to IE-1. The same HLA-C allotype specifically protected infected cells from attack by NK cells that expressed a corresponding HLA-C-specific KIR. Thus, allotype-specific viral immunoevasion allows HCMV to escape control by NK cells and HLA-A- and HLA-B-restricted T cells, while the virus becomes selectively vulnerable to an immunodominant population of HLA-C-restricted T cells. Our work identifies a T cell population that may be of particular efficiency in HCMV-specific immunotherapy.
MHC Multimer-Guided and Cell Culture-Independent Isolation of Functional T Cell Receptors from Single Cells Facilitates TCR Identification for Immunotherapy
Georg D?ssinger, Mario Bunse, Jeannette Bet, Julia Albrecht, Paulina J. Paszkiewicz, Bianca Wei?brich, Isabell Schiedewitz, Lynette Henkel, Matthias Schiemann, Michael Neuenhahn, Wolfgang Uckert, Dirk H. Busch
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0061384
Abstract: Adoptive therapy using T cells redirected to target tumor- or infection-associated antigens is a promising strategy that has curative potential and broad applicability. In order to accelerate the screening process for suitable antigen-specific T cell receptors (TCRs), we developed a new approach circumventing conventional in vitro expansion-based strategies. Direct isolation of paired full-length TCR sequences from non-expanded antigen-specific T cells was achieved by the establishment of a highly sensitive PCR-based T cell receptor single cell analysis method (TCR-SCAN). Using MHC multimer-labeled and single cell-sorted HCMV-specific T cells we demonstrate a high efficacy (approximately 25%) and target specificity of TCR-SCAN receptor identification. In combination with MHC-multimer based pre-enrichment steps, we were able to isolate TCRs specific for the oncogenes Her2/neu and WT1 even from very small populations (original precursor frequencies of down to 0.00005% of CD3+ T cells) without any cell culture step involved. Genetic re-expression of isolated receptors demonstrates their functionality and target specificity. We believe that this new strategy of TCR identification may provide broad access to specific TCRs for therapeutically relevant T cell epitopes.
Rapid, Non-Destructive, Textile Classification Using SIMCA on Diffuse Near-Infrared Reflectance Spectra  [PDF]
Christopher B. Davis, Kenneth W. Busch, Dennis H. Rabbe, Marianna A. Busch, Judith R. Lusk
Journal of Modern Physics (JMP) , 2015, DOI: 10.4236/jmp.2015.66076
Abstract: Soft independent modeling of class analogy (SIMCA) was successful in classifying a large library of 758 commercially available, non-blended samples of acetate, cotton, polyester, rayon, silk and wool 89% - 98% of the time at the 95% confidence level (p = 0.05 significance level). In the present study, cotton and silk had a 62% and 24% chance, respectively, of being classified with their own group and also with rayon. SIMCA correctly identified a counterfeit “silk” sample as polyester. When coupled with diffuse NIR reflectance spectroscopy and a large sample library, SIMCA shows considerable promise as a quick, non-destructive, multivariate method for fiber identification. A major advantage is simplicity. No sample pretreatment of any kind was required, and no adjust-ments were made for fiber origin, manufacturing process residues, topical finishes, weave pattern, or dye content. Increasing the sample library should make the models more robust and improve identification rates over those reported in this paper.
In Vivo Functional Requirement of the Mouse Ifitm1 Gene for Germ Cell Development, Interferon Mediated Immune Response and Somitogenesis
Ingeborg Klymiuk, Lukas Kenner, Thure Adler, Dirk H. Busch, Auke Boersma, Martin Irmler, Valérie Gailus-Durner, Helmut Fuchs, Nicole Leitner, Mathias Müller, Ralf Kühn, Michaela Schlederer, Irina Treise, Martin Hrabě de Angelis, Johannes Beckers
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0044609
Abstract: The mammalian Interferon induced transmembrane protein 1 (Ifitm1) gene was originally identified as a member of a gene family highly inducible by type I and type II interferons. Based on expression analyses, it was suggested to be required for normal primordial germ cell migration. The knockdown of Ifitm1 in mouse embryos provided evidence for a role in somitogenesis. We generated the first targeted knockin allele of the Ifitm1 gene to systematically reassess all inferred functions. Sperm motility and the fertility of male and female mutant mice are as in wild type littermates. Embryonic somites and the adult vertebral column appear normal in homozygous Ifitm1 knockout mice, demonstrating that Ifitm1 is not essential for normal segmentation of the paraxial mesoderm. Proportions of leucocyte subsets, including granulocytes, monocytes, B-cells, T-cells, NK-cells, and NKT-cells, are unchanged in mutant mice. Based on a normal immune response to Listeria monocytogenes infection, there is no evidence for a dysfunction in downstream IFNγ signaling in Ifitm1 mutant mice. Expression from the Ifitm1 locus from E8.5 to E14.5 is highly dynamic. In contrast, in adult mice, Ifitm1 expression is highly restricted and strong in the bronchial epithelium. Intriguingly, IFITM1 is highly overexpressed in tumor epithelia cells of human squamous cell carcinomas and in adenocarcinomas of NSCLC patients. These analyses underline the general importance of targeted in vivo studies for the functional annotation of the mammalian genome. The first comprehensive description of the Ifitm1 expression pattern provides a rational basis for the further examination of Ifitm1 gene functions. Based on our data, the fact that IFITM1 can function as a negative regulator of cell proliferation, and because the gene maps to chromosome band 11p15.5, previously associated with NSCLC, it is likely that IFITM1 in man has a key role in tumor formation.
Novel Serial Positive Enrichment Technology Enables Clinical Multiparameter Cell Sorting
Christian Stemberger, Stefan Dreher, Claudia Tschulik, Christine Piossek, Jeannette Bet, Tori N. Yamamoto, Matthias Schiemann, Michael Neuenhahn, Klaus Martin, Martin Schlapschy, Arne Skerra, Thomas Schmidt, Matthias Edinger, Stanley R. Riddell, Lothar Germeroth, Dirk H. Busch
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0035798
Abstract: A general obstacle for clinical cell preparations is limited purity, which causes variability in the quality and potency of cell products and might be responsible for negative side effects due to unwanted contaminants. Highly pure populations can be obtained best using positive selection techniques. However, in many cases target cell populations need to be segregated from other cells by combinations of multiple markers, which is still difficult to achieve – especially for clinical cell products. Therefore, we have generated low-affinity antibody-derived Fab-fragments, which stain like parental antibodies when multimerized via Strep-tag and Strep-Tactin, but can subsequently be removed entirely from the target cell population. Such reagents can be generated for virtually any antigen and can be used for sequential positive enrichment steps via paramagnetic beads. First protocols for multiparameter enrichment of two clinically relevant cell populations, CD4high/CD25high/CD45RAhigh ‘regulatory T cells’ and CD8high/CD62Lhigh/CD45RAneg ‘central memory T cells’, have been established to determine quality and efficacy parameters of this novel technology, which should have broad applicability for clinical cell sorting as well as basic research.
Onwards and upwards: European Journal of Medical Research continues as an open access publication
Stefan Busch, Dieter H?ussinger
European Journal of Medical Research , 2012, DOI: 10.1186/2047-783x-17-1
Abstract: As of today, at the outset of its 17th volume, the European Journal of Medical Research is an open access publication, having joined BioMed Central's portfolio of journals. The change in the publishing model awards this well-established title with an opportunity to develop into a leading general medicine journal over the coming years.Founded by the Munich-based publishing house Holzapfel Verlag in 1995, the journal soon became a respected and broadly indexed resource. Until the end of 2011, however, the journal remained a print-only publication. While many other aspects of the journal will continue without change, the publishing 'format' is now changing, from print-only to online-only and from subscription-based economics to the open access model with article processing charges borne, after peer review and upon acceptance, by authors' home institutions or research funders. The rapid growth of high-quality open access publications is rooted in the fact that an increasing number of universities, funding agencies and governmental agencies support or even mandate open access, in different ways and through different means.The journal's new publisher, BioMed Central (Springer's imprint for open access journals in biology and medical disciplines) has over recent years accumulated a wealth of experience with journal transfers and conversions to open access. A rapidly growing number of journals in BioMed Central's portfolio moved there from other publishing arrangements. In such cases, a clear trend has emerged that shows an increase of these journals' impact factors after two to three years when the open access articles start forming the basis of the calculations. Higher visibility and unrestricted access lead to increased impact [1], of which the impact factor is only one aspect. Taken as a proxy, however, it serves as an indicator of the effect of open access on visibility and usage. Cases in point are Acta Veterinaria Scandinavica, which has seen its impact factor quadru
Hydraulic Transport Across Hydrophilic and Hydrophobic Nanopores: Flow Experiments with Water and n-Hexane
Simon Gruener,Dirk Wallacher,Stefanie Greulich,Mark Busch,Patrick Huber
Physics , 2015,
Abstract: We experimentally explore pressure-driven flow of water and n-hexane across nanoporous silica (Vycor glass monoliths with 7 or 10 nm pore diameters, respectively) as a function of temperature and surface functionalization (native and silanized glass surfaces). Hydraulic flow rates are measured by applying hydrostatic pressures via inert gases (argon and helium, pressurized up to 70 bar) on the upstream side in a capacitor-based membrane permeability setup. For the native, hydrophilic silica walls, the measured hydraulic permeabilities can be quantitatively accounted for by bulk fluidity provided we assume a sticking boundary layer, i.e. a negative velocity slip length of molecular dimensions. The thickness of this boundary layer is discussed with regard to previous capillarity-driven flow experiments (spontaneous imbibition) and with regard to velocity slippage at the pore walls resulting from dissolved gas. Water flow across the silanized, hydrophobic nanopores is blocked up to a hydrostatic pressure of at least 70 bar. The absence of a sticking boundary layer quantitatively accounts for an enhanced n-hexane permeability in the hydrophobic compared to the hydrophilic nanopores.
Dll1 Haploinsufficiency in Adult Mice Leads to a Complex Phenotype Affecting Metabolic and Immunological Processes
Isabel Rubio-Aliaga, Gerhard K. H. Przemeck, Helmut Fuchs, Valérie Gailus-Durner, Thure Adler, Wolfgang Hans, Marion Horsch, Birgit Rathkolb, Jan Rozman, Anja Schrewe, Sibylle Wagner, Sabine M. Hoelter, Lore Becker, Thomas Klopstock, Wolfgang Wurst, Eckhard Wolf, Martin Klingenspor, Boris T. Ivandic, Dirk H. Busch, Johannes Beckers, Martin Hrabé de Angelis
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0006054
Abstract: Background The Notch signaling pathway is an evolutionary conserved signal transduction pathway involved in embryonic patterning and regulation of cell fates during development and self-renewal. Recent studies have demonstrated that this pathway is integral to a complex system of interactions, involving as well other signal transduction pathways, and implicated in distinct human diseases. Delta-like 1 (Dll1) is one of the known ligands of the Notch receptors. The role of the Notch ligands is less well understood. Loss-of-function of Dll1 leads to embryonic lethality, but reduction of Delta-like 1 protein levels has not been studied in adult stage. Methodology/Principal Findings Here we present the haploinsufficient phenotype of Dll1 and a missense mutant Dll1 allele (Dll1C413Y). Haploinsufficiency leads to a complex phenotype with several biological processes altered. These alterations reveal the importance of Dll1 mainly in metabolism, energy balance and in immunology. The animals are smaller, lighter, with altered fat to lean ratio and have increased blood pressure and a slight bradycardia. The animals have reduced cholesterol and triglyceride levels in blood. At the immunological level a subtle phenotype is observed due to the effect and fine-tuning of the signaling network at the different levels of differentiation, proliferation and function of lymphocytes. Moreover, the importance of the proteolytic regulation of the Notch signaling network emphasized. Conclusions/Significance In conclusion, slight alterations in one player of Notch signaling alter the entire organism, emphasizing the fine-tuning character of this pathway in a high number of processes.
The Endocytic Adaptor Eps15 Controls Marginal Zone B Cell Numbers
Benedetta Pozzi, Stefania Amodio, Caterina Lucano, Anna Sciullo, Simona Ronzoni, Daniela Castelletti, Thure Adler, Irina Treise, Ingrid Holmberg Betsholtz, Birgit Rathkolb, Dirk H. Busch, Eckhard Wolf, Helmut Fuchs, Valérie Gailus-Durner, Martin Hrabě de Angelis, Christer Betsholtz, Stefano Casola, Pier Paolo Di Fiore, Nina Offenh?user
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0050818
Abstract: Eps15 is an endocytic adaptor protein involved in clathrin and non-clathrin mediated endocytosis. In Caenorhabditis elegans and Drosophila melanogaster lack of Eps15 leads to defects in synaptic vesicle recycling and synapse formation. We generated Eps15-KO mice to investigate its function in mammals. Eps15-KO mice are born at the expected Mendelian ratio and are fertile. Using a large-scale phenotype screen covering more than 300 parameters correlated to human disease, we found that Eps15-KO mice did not show any sign of disease or neural deficits. Instead, altered blood parameters pointed to an immunological defect. By competitive bone marrow transplantation we demonstrated that Eps15-KO hematopoietic precursor cells were more efficient than the WT counterparts in repopulating B220+ bone marrow cells, CD19? thymocytes and splenic marginal zone (MZ) B cells. Eps15-KO mice showed a 2-fold increase in MZ B cell numbers when compared with controls. Using reverse bone marrow transplantation, we found that Eps15 regulates MZ B cell numbers in a cell autonomous manner. FACS analysis showed that although MZ B cells were increased in Eps15-KO mice, transitional and pre-MZ B cell numbers were unaffected. The increase in MZ B cell numbers in Eps15 KO mice was not dependent on altered BCR signaling or Notch activity. In conclusion, in mammals, the endocytic adaptor protein Eps15 is a regulator of B-cell lymphopoiesis.
Standardized, Systemic Phenotypic Analysis of UmodC93F and UmodA227T Mutant Mice
Elisabeth Kemter, Petra Prückl, Birgit Rathkolb, Kateryna Micklich, Thure Adler, Lore Becker, Johannes Beckers, Dirk H. Busch, Alexander A. G?tz, Wolfgang Hans, Marion Horsch, Boris Ivandic, Martin Klingenspor, Thomas Klopstock, Jan Rozman, Anja Schrewe, Holger Schulz, Helmut Fuchs, Valérie Gailus-Durner, Martin Hrabé de Angelis, Eckhard Wolf, Bernhard Aigner
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0078337
Abstract: Uromodulin-associated kidney disease (UAKD) summarizes different clinical features of an autosomal dominant heritable disease syndrome in humans with a proven uromodulin (UMOD) mutation involved. It is often characterized by hyperuricemia, gout, alteration of urine concentrating ability, as well as a variable rate of disease progression inconstantly leading to renal failure and histological alterations of the kidneys. We recently established the two Umod mutant mouse lines UmodC93F and UmodA227T on the C3H inbred genetic background both showing kidney defects analogous to those found in human UAKD patients. In addition, disease symptoms were revealed that were not yet described in other published mouse models of UAKD. To examine if further organ systems and/or metabolic pathways are affected by Umod mutations as primary or secondary effects, we describe a standardized, systemic phenotypic analysis of the two mutant mouse lines UmodA227T and UmodC93F in the German Mouse Clinic. Different genotypes as well as different ages were tested. Beside the already published changes in body weight, body composition and bone metabolism, the influence of the Umod mutation on energy metabolism was confirmed. Hematological analysis revealed a moderate microcytic and erythropenic anemia in older Umod mutant mice. Data of the other analyses in 7-10 month-old mutant mice showed single small additional effects.
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